We propose to continue studying the intermediate filament (IF) based cytoskeletal system in mammalian cells. Emphasis will be placed on the regulation of the organization of IF and their interactions with the nuclear surface. The long term goal of these studies is to determine the possible functions of the IF system and its interaction with the nucleus, now known to contain another IF protein family system known as the nuclear lamins. The experimental plan involves detailed morphological studies on the coordinated activities of the cytoplasmic IF and nuclear surface systems throughout the cell cycle using immunocytochemical techniques, biochemical and physiological analyses, the effects of phosphorylation on the cytoplasmic IF system, structural studies of the nuclear lamin paracrystals, and the use of microinjection of derivatized IF proteins. The IF system is thought to be involved in various physiological activities, including nuclear-cytoplasmic interactions, signal processing between the cell surface and the nucleus, etc. With regard to disease processes, this system is frequently found in an altered state in many diseases including cancer, Alzheimers disease, liver diseases and several other neurological disorders.